Rescue of a Dictyostelium discoideum mutant defective in cyclic nucleotide phosphodiesterase

Faure, Michel; Podgorski, Gregory J.; Franke, Jakob; Kessin, Richard H.

doi:10.1016/s0012-1606(89)80010-7

Cited by 26 publications

(10 citation statements)

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“…These two promoters allow a temporal and spatial regulation of phosphodiesterase production. This is critical, since an excess or a lack of phosphodiesterase blocks late development (10,11). The cAMP inducibility of the aggregation-specific promoter is consistent with the role of the enzyme during aggregation.…”

Section: Discussionsupporting

confidence: 55%

“…There is growing evidence that chemotaxis toward cAMP directs the movements of the multicellular structure that is formed after aggregation (43,46) and that extracellular cAMP is involved in the differentiation of prespore cells (54). We have shown that the presence of phosphodiesterase is required for proper formation of fruiting bodies (11) and that an excess of phosphodiesterase during late development blocks morphogenesis (10). In this work, we complete the description of the structure of the phosphodiesterase gene previously reported (37) and show that the importance of the phosphodiesterase in D. discoideum development is reflected in the complex structure and regulation of the gene.…”

Section: Discussionmentioning

confidence: 66%

“…Complete development can be restored by production of the enzyme from the cloned gene, introduced into the cells by transformation (11). The phosphodiesterase plays a role in late development when chemotaxis is involved in morphogenesis leading to fruiting body formation (43,45).…”

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confidence: 99%

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The cyclic nucleotide phosphodiesterase gene of Dictyostelium discoideum contains three promoters specific for growth, aggregation, and late development.

Faure¹,

Franke²,

Hall³

et al. 1990

Mol. Cell. Biol.

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The cyclic nucleotide phosphodiesterase (phosphodiesterase) plays essential roles throughout the development of Dictyostelium discoideum. It is crucial to cellular aggregation and to postaggregation morphogenesis. The phosphodiesterase gene is transcribed into three mRNAs, containing the same coding sequence connected to different 5' untranslated sequences, that accumulate at different times during the life cycle. A 1.9-kilobase (kb) mRNA is specific for growth, a 2.4-kb mRNA is specific for aggregation, and a 2.2-kb mRNA is specific for late development and is only expressed in prestalk cells. Hybridization of RNA isolated from cells at various stages of development with different upstream regions of the gene indicated separate promoters for each of the three mRNAs. The existence of specific promoters was confirmed by fusing the three putative promoter regions to the chloramphenicol acetyltransferase reporter gene, and the analysis of transformants containing these constructs. The three promoters are scattered within a 4.1-kilobase pair (kbp) region upstream of the initiation codon. The late promoter is proximal to the coding sequence, the growth-specific promoter has an initiation site that is 1.9 kbp upstream of the ATG codon, and the aggregation-specific promoter has an initiation site 3 kbp upstream.When Dictyostelium discoideum amoebae are deprived of nutrients, they initiate a developmental program that results in the formation of a multicellular organism composed of differentiated cell types. The aggregation process that takes place early in development is driven by chemotaxis toward cyclic AMP (cAMP) (6), and one of the earliest events in development is the elaboration of the biochemical apparatus required for chemotaxis toward cAMP (for reviews see references 7, 18, and 23). Soon after starvation, the cells synthesize an adenylate cyclase, a cell surface cAMP receptor, an extracellular phosphodiesterase, and a specific phosphodiesterase inhibitor. These proteins, among others, function coordinately to allow the cells to aggregate by chemotaxis. Cells secrete pulses of cAMP every 5 to 6 min, and neighboring cells respond by moving toward elevated concentrations of cAMP and by emitting cAMP to create a relay. The binding of cAMP to cell surface receptors activates second messenger cascades involving G proteins (27) that lead to a variety of cellular events (for reviews, see references 13 and 20), including the chemotactic response and the regulation of genes specific for development. The cAMP receptor is down regulated and phosphorylated upon constant stimulation by cAMP (25,53), and this results in the adaptation of cellular responses (52). The cyclic nucleotide phosphodiesterase (phosphodiesterase) acts outside the cell to reduce cAMP levels, limiting saturation and down regulation of the receptor. The phosphodiesterase exists in membrane-bound and free extracellular forms (30, 47). Its activity is regulated at the gene level (16) and is controlled at the protein level by a specific inhibitor (15). A m...

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 66%

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The cyclic nucleotide phosphodiesterase gene of Dictyostelium discoideum contains three promoters specific for growth, aggregation, and late development.

Faure¹,

Franke²,

Hall³

et al. 1990

Mol. Cell. Biol.

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“…(Barra et al, 1980;Sucgang et al, 1997). This phenotype can be rescued by the re-expression of PdsA; however, overexpression leads to aberrant development (Darmon et al, 1978;Faure et al, 1988Faure et al, , 1989. PdsA has been purified from cells and has been extensively characterized biochemically Brown and Rutherford, 1980;Blondelet and Brachet, 1981;Yamasaki and Hayashi, 1982;Franke and Kessin, 1992).…”

Section: Introductionmentioning

confidence: 99%

The Group Migration of Dictyostelium Cells Is Regulated by Extracellular Chemoattractant Degradation

Garcia

Rericha

Heger

et al. 2009

MBoC

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Starvation of Dictyostelium induces a developmental program in which cells form an aggregate that eventually differentiates into a multicellular structure. The aggregate formation is mediated by directional migration of individual cells that quickly transition to group migration in which cells align in a head-to-tail manner to form streams. Cyclic AMP acts as a chemoattractant and its production, secretion, and degradation are highly regulated. A key protein is the extracellular phosphodiesterase PdsA. In this study we examine the role and localization of PdsA during chemotaxis and streaming. We find that pdsA ؊ cells respond chemotactically to a narrower range of chemoattractant concentrations compared with wild-type (WT) cells. Moreover, unlike WT cells, pdsA ؊ cells do not form streams at low cell densities and form unusual thick and transient streams at high cell densities. We find that the intracellular pool of PdsA is localized to the endoplasmic reticulum, which may provide a compartment for storage and secretion of PdsA. Because we find that cAMP synthesis is normal in cells lacking PdsA, we conclude that signal degradation regulates the external cAMP gradient field generation and that the group migration behavior of these cells is compromised even though their signaling machinery is intact. INTRODUCTIONThe process by which cells sense an attractant molecule and respond by migrating directionally toward it is called chemotaxis. Chemotaxis is essential for a variety of physiological processes in mammals as well as for the survival of lower eukaryotes. The mechanisms that regulate the directed migration of neutrophils and Dictyostelium discoideum have been extensively studied previously (van Haastert and Devreotes, 2004;Bagorda et al., 2006;Friedl and Weigelin, 2008;Stephens et al., 2008). One particular challenge of these fast-moving cells is to maintain the ability to respond sensitively and rapidly to an attractant signal. Because both neutrophils and Dictyostelium cells use signal relay loops to propagate chemoattractant signals, mechanisms must be at play to maintain detectable levels of chemoattractants. Remarkably, signal degradation also seems to play an important role in the developmental processes of multicellular organisms. Migration of primordial germ cells in Drosophila and Zebrafish seems to require degradation of specific lysophospholipids in the former or chemokines in the latter to allow these cells to find their proper developmental environment (Renault and Lehmann, 2006;Minina et al., 2007). Many cell types use receptor-mediated degradation to maintain detectable levels of chemoattractants. In this context, cells internalize the bound receptor and as part of the receptor recycling pathway the ligand is released for degradation (Minina et al., 2007;Boldajipour et al., 2008;Borroni et al., 2008;Scola et al., 2008). Alternatively, extracellular enzymes can specifically degrade the extracellular signaling molecules, allowing the sensing machinery to go back to basal levels and retain high se...

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“…When there is a high density of starving cells and thus a high concentration of CMF, the cells aggregate by use of relayed pulses of cAMP as a chemoattractant (for review, see Robertson and Grutsch 1981). Starving cells also secrete a phosphodiesterase and a phosphodiesterase inhibitor; the phosphodiesterase causes the levels of cAMP to return to a baseline level in the interval between pulses (Riedel and Gerisch 1971;Dicou and Brachet 1979;Kessin et al 1979;Tsang and Coukell 1979;Franke and Kessin 1981;Orlow et al 1981;Faure et al 1988Faure et al , 1989Hall et al 1993;Wu et al 1995) and also steepens the cAMP gradient sensed by the cell (Nanjundiah and Malchow 1976). The aggregate forms a migrating slug, which, in turn, forms a fruiting body containing a mass of spore cells supported by a column of stalk cells (for review, see Loomis 1975Loomis , 1993Devreotes 1989;Schaap 1991;Firtel 1995).…”

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confidence: 99%

A cell-counting factor regulating structure size in Dictyostelium

Brock¹,

Gomer²

1999

Genes & Development

123

187

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Developing Dictyostelium cells form large aggregation streams that break up into groups of 0.2 × 10 5 to 1 × 10 5 cells. Each group then becomes a fruiting body. smlA cells oversecrete an unknown factor that causes aggregation streams to break up into groups of ∼5 × 10 3 cells and thus form very small fruiting bodies. We have purified the counting factor and find that it behaves as a complex of polypeptides with an effective molecular mass of 450 kD. One of the polypeptides is a 40-kD hydrophilic protein we have named countin. In transformants with a disrupted countin gene, there is no detectable secretion of counting factor, and the aggregation streams do not break up, resulting in huge (up to 2 × 10 5 cell) fruiting bodies.

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Rescue of a Dictyostelium discoideum mutant defective in cyclic nucleotide phosphodiesterase

Cited by 26 publications

References 26 publications

The cyclic nucleotide phosphodiesterase gene of Dictyostelium discoideum contains three promoters specific for growth, aggregation, and late development.

The cyclic nucleotide phosphodiesterase gene of Dictyostelium discoideum contains three promoters specific for growth, aggregation, and late development.

The Group Migration of Dictyostelium Cells Is Regulated by Extracellular Chemoattractant Degradation

A cell-counting factor regulating structure size in Dictyostelium

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